TGF-β as Predictive Marker and Pharmacological Target in Lung Cancer Approach

Ramundo, Valeria; Palazzo, Maria Luisa; Aldieri, Elisabetta

doi:10.3390/cancers15082295

Cited by 8 publications

(2 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The targeting of TGF-β1, which is abundant in platelet α-granules, represents another strategy that not only regulates the pro-tumorigenic activity of these cells but also attenuates the resistance of lung cancer to PD-1/PD-L1-directed immunotherapy [150][151][152]. Importantly, in this context, advanced lung cancer is associated with elevated systemic levels of TGF-β1 [153,154].…”

Section: Transforming Growth Factor β1mentioning

confidence: 99%

Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer

Rapoport

Steel

Theron

2023

IJMS

View full text Add to dashboard Cite

Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs in the blood of lung cancer patients has been associated with tumor growth, invasion, angiogenesis and metastasis, which correlate with disease progression and decreased survival times. The final section of the review addresses, firstly, the role of cancer-related platelet activation and thrombosis in the pathogenesis of secondary cardiovascular disorders and the associated mortality, particularly in lung cancer, which is second only to disease progression; secondly, the review addresses the potential role of antiplatelet agents in the adjunctive therapy of cancer.

show abstract

Section: Transforming Growth Factor β1mentioning

confidence: 99%

Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer

Rapoport

Steel

Theron

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Further, extensive research has been conducted to identify predictive biomarkers for the initial ICI response. Tumor programmed death ligand-1 (PD-L1) expression, the tumor mutational burden (TMB), deficient mismatch repair, tumor infiltrating lymphocytes, and related gene expression signatures have been identified as potential predictors, and various other markers are under investigation ( 6 - 12 ). However, due to tumor heterogeneity, sampling bias, antibody discrepancy, and the poor feasibility of dynamic monitoring, obvious limitations exist among these biomarkers.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 mRNA derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer

Hu,

Wang,

Zhang

et al. 2024

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background To date, the role of programmed death ligand-1 (PD-L1) messenger RNA (mRNA) derived from tumor-educated platelets (TEPs) has not been well investigated in patients with advanced non-small cell lung cancer (NSCLC). A few reports have examined whether mRNA in TEPs can predict the clinical responses of patients with advanced NSCLC following immunotherapy. This study aimed to identify novel biomarkers to improve the clinical benefits and outcomes of NSCLC patients. Methods Advanced NSCLC patients receiving a combination of immunotherapy and chemotherapy, or immunotherapy alone as a first- or second-line treatment at the Fudan University Shanghai Cancer Center were enrolled in this study. All the patients had wild-type epidermal growth factor receptor/anaplastic lymphoma kinase. The patients were enrolled in clinical trials for immune checkpoint inhibitors (ICIs), including nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, and camrelizumab. Tumoral PD-L1 expression was tested by immunohistochemistry (PD-L1 22C3 pharmDx kit, Agilent, Santa Clara, CA, USA) in archived tissue samples, when available, to calculate the tumor proportion scores (TPSs). RNA and exosomal RNA of blood were isolated before immunotherapy using the Yunying RNA extraction kit (Yunying Medicine, Shanghai, China). The concentration and quality of the RNA was determined using a Qubit fluorometer (Life Technologies, Carlsbad, CA, USA). Finally, we analyzed the predictive value of TEP-derived PD-L1 mRNA expression and association with the level of the tumoral PD-L1 expression. Results In total, 72 patients were enrolled in this study. Most of the patients were male (n=54, 75.0%), had adenocarcinoma (n=49, 68.1%). We found there was no significant correlation between the TEP-derived mRNA of PD-L1 and tumoral PD-L1 expression based on the results of the Pearson Correlation test (r=−0.19, P=0.233). Based on the median of PD-L1 mRNA, 72 patients were divided into a high PD-L1 group and a low PD-L1 group. We found that 19 patients (44.4%) responded to immunotherapy [partial response or progression-free survival (PFS) >6 months] in the high PD-L1 group, but only five patients (13.9%) responded to immunotherapy in the low PD-L1 group (P<0.01). The median PFS of the low PD-L1 group was lower than that of the high PD-L1 group (2.8 vs. 8.3 months, P<0.001). For the patients who were treated with immunotherapy alone (n=64), a similar PFS advantage was observed in the high PD-L1 group (2.8 vs. 8.0 months, P=0.002). Conclusions This article presented the first data on TEP-derived PD-L1 mRNA in advanced NSCLC patients following immunotherapy and showed the potential advantage of using it as the surrogate biomarker for predicting the PFS and overall survival of patients following immunotherapy.

show abstract

COX‐2 in lung cancer: Mechanisms, development, and targeted therapies

Liu,

Zhang,

Sun

et al. 2024

Chronic Diseases and Translational Medicine

View full text Add to dashboard Cite

Lung cancer (LC) is the leading cause of cancer‐related death worldwide, with non‐small cell lung cancer (NSCLC) comprising 85% of all cases. COX‐2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX‐2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX‐2 holds potential as a predictive marker for early‐stage NSCLC, guiding targeted therapy in patients with early COX‐2 overexpression. Additionally, combining COX‐2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX‐2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.

show abstract

TGF-β as Predictive Marker and Pharmacological Target in Lung Cancer Approach

Cited by 8 publications

References 81 publications

Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer

Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer

PD-L1 mRNA derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer

COX‐2 in lung cancer: Mechanisms, development, and targeted therapies

Contact Info

Product

Resources

About